APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice.

Scientific Reports
Estela Area-GomezTal Nuriel

Abstract

The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason for the association between APOE4 and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing that APOE4 negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of APOE4's role in AD pathogenesis, we performed a transcriptomics analysis of APOE4 vs. APOE3 expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of aged APOE mice. This study revealed EC-specific upregulation of genes related to oxidative phosphorylation (OxPhos). Follow-up analysis utilizing the Seahorse platform showed decreased mitochondrial respiration with age in the hippocampus and cortex of APOE4 vs. APOE3 mice, but not in the EC of these mice. Additional studies, as well as the original transcriptomics data, suggest that multiple bioenergetic pathways are differentially regulated by APOE4 expression in the EC of aged APOE mice in order to increase the mitochondrial coupling efficiency...Continue Reading

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Citations

Sep 5, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Alexandra J WeigandUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Sep 24, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Elizabeth E BlueAlexander P Reiner
Nov 9, 2020·Trends in Neurosciences·Maria Calvo-Rodriguez, Brian J Bacskai
Feb 9, 2021·Reviews in the Neurosciences·Asiamah Ernest AmponsahHuixian Cui
Sep 28, 2021·American Journal of Physiology. Endocrinology and Metabolism·K Allison AmickAnthony J A Molina
Nov 8, 2021·Molecular Neurodegeneration·Hans-Ulrich KleinPhilip L De Jager

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Methods Mentioned

BETA
NMR
nuclear magnetic resonance
RNA-Seq
Assay
protein assay
Profiler

Software Mentioned

Profinder
HT
Bowtie
LCModel
Agilent Profinder
PIUMet
Seahorse
Mass Profiler Professional
Bioconductor
ggplot2

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